Accidental Poisoning with the Antihistamine Drug "histantin"

?hild, who died in hospital three days before her first birthday. The father is a man in ftls early thirties, who owns a shop. The mother is a kind and pleasant woman of some ^venty years of age. They live in a small house over the shop. Mother has a mild ton. disorder for which, unfortunately, as events will show, she was taking anti-^lstamine tablets ("Histantin"). She came into the room where Jane had been left playing one day and found her eating some tablets. Mother thinks that nine were swallowed in all. The child was Seen by a doctor about one hour later. There had been no vomiting and Jane seemed ^VeU, so the doctor advised that she be taken home to rest. Fifteen minutes later she started to vomit and had generalised convulsions. She was immediately taken to the local hospital where her stomach was washed out. ltn bicarbonate of soda solution, approximately one-and-three-quarters hour after lrigestion of the tablets. While this was proceeding the doctor telephoned me. With a jecent previous experience of such a case (a child who also died despite treatment) advised that Jane should be brought into hospital immediately. The journey was A?ng one and she arrived in hospital some four hours after swallowing the tablets.

eating some tablets. Mother thinks that nine were swallowed in all. The child was Seen by a doctor about one hour later. There had been no vomiting and Jane seemed ^VeU, so the doctor advised that she be taken home to rest. Fifteen minutes later she started to vomit and had generalised convulsions.
She was immediately taken to the local hospital where her stomach was washed out . ltn bicarbonate of soda solution, approximately one-and-three-quarters hour after lrigestion of the tablets. While this was proceeding the doctor telephoned me. With a jecent previous experience of such a case (a child who also died despite treatment) advised that Jane should be brought into hospital immediately. The journey was A?ng one and she arrived in hospital some four hours after swallowing the tablets.
On admission she was slightly cyanosed and generalised muscular twitching was een. Her temperature was ioo-8?. The heart rate varied between 80 and 170 and was regular (presumably owing to the so-called quinidine effect of the drug). Moist 0lJnds were heard all over the lungs, an ominous sign which carries a very grave Pr?gnosis in this condition.
TREATMENT AND PROGRESS ~ The stomach was sucked out, and some paraldehyde was injected intramuscularly. 7e Was put in an oxygen tent. We were faced here with the problem of dealing ! n a condition in which central nervous depression may prove lethal, yet nervous filiation may produce fits which are themselves highly dangerous. The problem of lrnulants versus anticonvulsants is an insoluble one, but in this case, as in other Ses of poisoning, the usual rule is to treat the immediate disturbance rather than the . erlying condition. Some forty-five minutes later, when the generalised twitching still marked, she was given rectal thiopentone. tK hours after admission the heart rate was rapid and irregular, she was vomiting 0j.lck brown material, and the twitching persisted. After a further small rectal injection thiopentone the twitching ceased, her colour became better and the respiratory Was lower. ^t this stage, the case was discussed with Professor Heller, who kindly came to the f>ital to see the child. Seven hours after admission convulsions recurred and ^ rther mild sedation was attempted. In spite of treatment the twitching persisted, ^.temperature rose to 105?, her general condition deteriorated and she developed ^Pheral circulatory failure and died some thirteen hours after admission to hospital. Dr. Apley. In paediatrics, as in general medicine, we tend to congratulate ourselve? on the fact that the incidence and dangers of many disorders, especially infections, a being rapidly controlled. Poisoning and accidents, in the home or on the road, a unfortunately not decreasing. I may add that dangerous iatrogenic disorders a seem to be increasing.
Medicines or pills are the cause of about half the deaths in children due to Only very rarely is this due to an error or accident by the doctor or chemist, others are due to the child swallowing liniments, cleaners, polishes, pesticides, e ' The most dangerous room in the house is the kitchen, followed in order by , bedroom, bathroom, and living room. The type of children affected can be divj into two groups. The first, and perhaps the most tragic, is the group of normal todd ^ with initiative and an urge to explore. In children, of course, the tongue is an organ sense. Any moveable object may be put into the mouth, but is often spat out a?. unless it is tasty. The difficulty is that more and more drugs are being made attrac to look at and palatable to swallow. Some of the NHS prescriptions are flavoured ^ extract of cherries, and so on, and some tablets are so like "Smarties" and "HunCvhie and Thousands", used to decorate cakes, that any child might be expected to goD them up (here a coloured slide, lent by Dr. Oppe, was shown to illustrate the simna ^ between tablets and sweets, (Plate II)). The second group, possibly larger than first, is made up of infants and toddlers who eat anything. They are fierce fee'^ both off the bottle or the breast, and will chew thumbs, fingers or anything they get hold of. This is said to be a form of self-gratification and has been claimed to part of a widespread psychological disturbance. f j Professor Hewer. Before we have any discussion of this case I shall ask Dr. Hal to tell us his autopsy findings. . f Dr. M. E. H. Half or d. The autopsy does not give us very much additional in . mation. There was some dehydration, with inelasticity of the skin. The liver, altno g normal in size, was flabby and pale. Histological examination confirmed that t was diffuse fatty change and also some early centrilobular necrosis. The kidneys sho ^ advanced cloudy swelling, but this may have been a post-mortem change sincetejy autopsy was performed twenty-three hours after death. The brain was modera oedematous, but there were no petechial haemorrhages.
There was no evidence of pre-existing disease or congenital deformity. ^ When allowance is made for the shorter second period, the increase is consider'1 and antihistamine drugs are second on the list. vhic^ There are two points of interest in the course of the illness of this child. One v ^ emerged during the inquest was that the first abnormality noticed was a vaca ^ pression. This has been observed in other reported cases of antihistamine PolS?orted The second point is the occurrence of vomiting; this is unusual. In the one reP.jj j^e case of Histantin poisoning3 vomiting also occurred. Perhaps Professor Heller^seda' able to explain these points. The reported case was successfully treated by Hgn tion atropine and amphetamine, although a large amount of the drug (900 mgnw been ingested. Dr with the effect of antihistamines on gastric secretion, found that ulcer patients tolerate these drugs rather badly and responded occasionally with an increase in ga ^ secretion. One may therefore conjecture that vomiting in a poisoned patient depe^ on the "competition" between central and peripheral action of the antihistaro1 drug. Secondly, the action of the antihistamine on the eyes has been mentioned, y would expect such effects since the antihistamines have quite pronounced atropine (or perhaps more correctly hyoscine) like properties. This brings me to central effects of the antihistamines. They, as Dr. Apley has 5 stressed, seem to consist in a curious mixture of depression and stimulation, I* ^ been suggested that the stimulant action is related to the atropine-like side effect afl^ it is of course true that belladonna poisoning may lead to central excitation aI) . pyrexia. But it should not be forgotten that antihistamines are also quite strong i0 1 anaesthetics and that local anaesthetics like cocaine and procaine have also a pronouneI1t stimulant effect on the central nervous system. However, remembering the under discussion whom?thanks to the kindness of Dr. Apley?I was able to see in , Children's Hospital, and the descriptions of some published cases of poisoning vv antihistamines, I have the impression that the central effects of these toxic doses c sist in a curious mixture of depression and stimulation of different parts of the t>r One is reminded of morphine although the cerebral localisation of these efect^ obviously different. The therapeutic problem is therefore?as already mentione very difficult. One really does not know which drugs to use to combat the toxic en ^ on the central nervous system. The history of this patient which, alas, resembles too closely that of many other cases of antihistamine poisoning in children, has le" ^ to the conclusion that more experimental work is needed to investigate the effeCt^ 3 toxic doses of antihistamines. I have, in fact, last week proposed this subject Ph.D. candidate. I think that we shall only arrive at a rational therapy if we K ^ which parts of the central nervous system are differentially affected by toxic d?s?s.^ antihistamines. Judging again from the comparison with morphine, we need somet like nalorphine that is to say a competitive inhibitor. .

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Lastly, a word about a further feature which was rather prominent in this Patl^rSt namely the effects on the heart. The quinidine-like action of antihistamines was ^ discovered in experiments on the isolated rabbit auricle. The present case sugg that it may not only be a pharmacological curiosity but a serious toxicological tea which requires therapeutical efforts. , fre Question. Is it logical to use histamine as a neurotransmitter for treatment 0 cerebral depression? rVes Professor Heller. There is good evidence that histamine is present in certain ne ^ but little evidence that it occurs in the central nervous system. Thus, it is un ^ to have a function as a central humoral transmitter. It is therefore difficult to see beneficial effects which injections of histamine could have in antihistamine pois ^ so far as the central nervous system is concerned. It may be useful, however, t0^zed out whether any of the peripheral effects of the antihistamines could be antag0 by histamine injections. uut Dr. Apley. Some say that histamine is useless and others that it should on no ac be given. , ajert Dr. W. O. Spence. What would be the dosage of antihistamine which shoui ^ ^ the general practitioner to take immediate action? I had a case two weeks ag? t toddler who swallowed about one ounce of Elixir Benadryl (about four times the c^ dose); I reassured the mother and left her to report again if any signs appear > it would appear as though it would have been safer to have made the child?rr^ Professor Heller. It is difficult to lay down maximum doses for the various c0 P.eI1cy with antihistaminic effects, not only because these substances have a different p? but also because the sensitivity of different patients to the same antihistamine varies widely. It may even vary considerably in the same patient according to n of health. May I refer you to the work of Warin4 who has shown by applyin& ^filial wheal tests that a patient may not be affected by the "ordinary" dose of an ^tihistaminic, but may need a very much larger dose to affect his allergic condition, however, I should like to stress that the wheal test in such a case is essential. br. B. E. McConnell. It is recorded that this child swallowed the drug at about ^ P-m. This was presumably after a meal. Would not an injection of apomorphine ave produced satisfactory emesis? Professor Heller. I would assume that apomorphine would be of value at an early a?e? e.g., before central depression has occurred. But I think that apomorphine ?uld be dangerous at a later stage since it has a medullary depressant action itself.
Or. x. E. Oppe. Gastric lavage is much more sure and also safer because with the e of an emetic there is a danger of aspiration pneumonia. j Y.ofessor Heller. I quite agree that an emetic may be dangerous. In that connection ^hink the simplest way of producing vomiting in a child, namely by insertion of a ^8er down its throat, should not be forgotten. vr? A. J. Webb. Emetics are very unpopular in the Casualty Department and ^ric lavage is always performed. j Ur. Halford. Mention has been made of the minimum lethal dose of antihistamines, j an account of a published series of fatal cases I found the smallest fatal dose was ?mgm. of methapyrilene hydrochloride ("Thenylene") for a child of sixteen ?nths: this is just twelve times the normal dose for such a child and only twice the dose.